2016年度 森基金研究成果報告書

パン酵母を用いた生体エネルギーが代謝ネットワークに与える影響の解明

生命情報科学(BI)
慶應義塾大学大学院  政策・メディア研究科
修士課程2年 馬場千聖

要旨

The biological system is controlled by complex regulatory network. This regulatory network responds to the external environment, controls gene expression under the influence of its signal, and monitors metabolism, thereby producing necessary energy and substances for itself. Regulation of environmental response and metabolism is responsible for most basic part to maintain life as a system, which is one of the essential features. These interactions are driven by intertwined biochemical reactions, resulting in complex dynamic responses such as molecular network level oscillations. A cell moves between phases of different cellular responses along with dynamic cell signal system switching between steady states. The sophisticated molecular networks that drive these phases have been studied in variety of fields. We have the enormous amount of available physiological data. Nevertheless, we are still far from the detailed understanding of cellular functions, because it is too complicated to understand it in fragments only. Here we deal with the relationship between energy consumption and production under different growth conditions. In particular, we focused on adenosine triphosphate (ATP), essential for cell proliferation and energy production. Therefore, we are investigated how growth rate, glucose feed and [ATP],[ATP]:[ADP] and energy charge influences the physiology of continuously grown bakers' yeast, using physiological, chemical and genetic approaches. In this study we used an accellerostat, where the dilution rate (growth rate) is changed continuously and oscillatory growth conditions (cells autosynchronise metabolic activity resulting in an large amplitude oscillation in [ATP]:[ADP]). We also examined chemical perturbation, dynamically changing glucose feed (dstat) and a synthetic doxycycline-inducible ATP-burning circuit. We concluded that maintenance energy can be defined using this experimental data when continuing to increase and decrease glucose flux without fixing growth rate. The new insight expected to be used as a useful finding of maintenance energy in cell physiology. We aimed to obtaining new findings on how the change in energy in the environment affects cell physiology. Our finding will provide the fundaments for further comprehension of energy availability in cellular physiology in the cell dynamics system, taking into account the mutual interaction of the systems. In particular, it may lead to important new concepts and insight into many issues such as Crabtree effect, aging and diabetes.


Keywords: 1. Yeast, 2. Change-stat, 3. Maintenance energy, 4. Environmental response, 5. ATP





研究業績
国際学会における発表

Baba C, Hesketh A, Tomita M and Murray DB., Modulation for the energetic state of continuously grown yeast by chemical and genetic approaches, Japan Q-Bio Week Tokyo Symposium, Jan 2015.

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